Abstract
Purpose :
Elevated intraocular pressure (IOP) is a prominent risk factor for primary open-angle glaucoma (POAG). Apolipoprotein E (APOE) is a major cholesterol carrier protein involved in the growth and repair of tissues. APOE is significantly implicated in Alzheimer’s disease (AD) pathogenesis and associated with POAG risk. In this study, we aimed at understanding the role of APOE in IOP homeostasis.
Methods :
In vivo effects of APOE on IOP were studied using wild-type (WT) and mice homozygous for the Apoetm1Unc knock-out (KO) mutation (ApoE-/-). Starting at day 66 postnatal, IOPs were measured using Tonolab every 20 days until 128 days postnatal in a blinded manner. Cohorts included 15 WT (8 males and 7 females) and 16 ApoE-/- (8 males and 8 females). Comparative analyses were conducted using unpaired t-test and patterns of significance (if p<0.05) were established.
Results :
In general, the average IOP in ApoE-/- mice was higher than the WT across measurements. The percentage increase in IOP in the ApoE-/- mice was between 4% to 18% higher compared to the WT (Figure 1A). A significant increase in the IOP of ApoE-/- mice compared to that of WT was observed starting at 108 days postnatal (p=.0015) and persisted at 128 days (p=0.0194) (Figure 1B). We did not see any significant difference in the male versus female cohorts for WT nor ApoE-/- mice.
Conclusions :
This preliminary longitudinal study reports for the first time the role of APOE in the IOP homeostasis. Interestingly, we did not find significant sex-dependent differences in IOP values between male and female even though sex dependent effects have been observed in the APOE correlation to AD pathogenesis. Further, mechanistic investigations into how the loss of APOE, or presence of specific allelic variants, causes or curtails IOP elevation will provide greater insights into specific APOE functions in TM tissue.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.